The prevalence of spina bifida has decreased since folic acid fortification, but an estimated 800 cases are born each year in the US to women who ingested at least the recommended daily amount (400 ug) of folic acid. Because spina bifida is a serious condition that has substantial impacts on families and society, further strategies for prevention are warranted. Using data collected in a large US case-control study from years 1988 to the present, preventable risk factors for folic acid-resistant spina bifida will be identified. The Boston University Slone Epidemiology Center Birth Defects Study is a unique resource with detailed data on mothers of spina bifida cases and controls for vitamin supplementation and dietary intakes. These data allow mothers to be classified according to sufficient or insufficient intake of folic acid during the periconceptional period. Further, detailed data are available on many other potential risk factors. The mothers of as many as 463 folic acid resistant spina bifida cases would be compared to two different control groups. One control group would comprise mothers of spina bifida offspring who ingested insufficient amounts of folic acid and the other would comprise mothers of non-malformed offspring who ingested sufficient amounts of folic acid. Comparisons will be made for factors that have previously been suggested as risk factors for neural tube defects or spina bifida, including obesity, diabetes, upper respiratory illness, fever, heat source exposure, infertility, assisted reproductive technology, smoking, alcohol, caffeine, and medication exposures. In addition, to hypothesis testing, all risk factor data, including all medications, illnesses, and nutrients, will be screened to identify new preventable risk factors.